Ethyl 3,6-di-O-benzyl-4-O-(9-fluorenylmethoxycarbonyl)-2-deoxy-2-(benzyloxycarbonyl)-amino-1-thio-β-D-glucopyranoside

Ethyl 3,6-di-O-benzyl-4-O-(9-fluorenylmethoxycarbonyl)-2-deoxy-2-(benzyloxycarbonyl)-amino-1-thio-β-D-glucopyranoside

Ethyl 3,6-di-O-benzyl-4-O-(9-fluorenylmethoxycarbonyl)-2-deoxy-2-(benzyloxycarbonyl)-amino-1-thio-β-D-glucopyranoside is a synthetic thioglycoside derivative designed for advanced carbohydrate chemistry applications. This compound integrates multiple protecting groups to enable controlled reactivity during oligosaccharide synthesis.

Chemical Structure

The molecule is based on a β-D-glucopyranoside scaffold with the following modifications:

• 1-Thioethyl group: Replaces the anomeric oxygen, forming a thioglycoside linkage that enhances stability and serves as a glycosyl donor in synthetic reactions. Thioglycosides are commonly synthesized using methods such as triflic acid-mediated reactions, which offer efficient synthesis pathways.
• 3,6-di-O-benzyl groups: Permanent benzyl ether protections at positions 3 and 6, providing stability under acidic/basic conditions and enabling selective deprotection later.
• 2-Deoxy-2-(benzyloxycarbonyl)-amino group: A 2-amino sugar derivative protected by a benzyloxycarbonyl (Cbz) group, which is acid-stable and removable via mild hydrolysis (e.g., hydrogenation).
• 4-O-Fmoc group: A 9-fluorenylmethoxycarbonyl (Fmoc) carbonate at position 4, acting as a temporary protecting group cleavable under basic conditions (e.g., piperidine).

Key Properties

• Molecular formula: Estimated to be C36H37NO8S\text{C}_{36}\text{H}_{37}\text{NO}_8\text{S}C36H37NO8S based on analogous structures.
• Stereochemistry: β-configuration at the anomeric center (C1), critical for mimicking biological glycosylation patterns.
• Role in synthesis:
  • The thioglycoside moiety facilitates activation via thiophilic promoters (e.g., NIS/TfOH) for glycosylation reactions.
  • Benzyl groups ensure regioselective reactivity, while Fmoc allows orthogonal deprotection for sequential glycosylation.
  • Cbz-protected amino group provides a versatile handle for post-synthetic modifications.

Applications

This compound is used in solid-phase oligosaccharide synthesis to build complex glycans. Its design supports iterative coupling cycles, where the Fmoc group is selectively removed to expose the 4-OH for subsequent glycosylation. Thioglycosides like this derivative are also explored as metabolic decoys to inhibit glycosylation processes.

Synthetic Considerations

• Preparation: Likely synthesized via sequential protection:
  1. Benzylation of glucose at positions 3 and 6.
  2. Fmoc protection at position 4.
  3. Cbz protection of the 2-amino group.
  4. Thioglycoside formation at the anomeric position, which can be achieved using efficient methods like triflic acid-mediated synthesis.
• Stability: Stable under standard glycosylation conditions but sensitive to conditions that cleave the Fmoc group.

This multifunctional building block exemplifies advanced strategies in glycochemistry, balancing stability and orthogonality for automated glycan assembly.

Citations:

1. https://pubs.rsc.org/en/content/getauthorversionpdf/c9ob01610d
2. https://pubmed.ncbi.nlm.nih.gov/1394300/
3. https://pubs.acs.org/doi/10.1021/jo00296a055
4. https://patents.google.com/patent/US20040019198A1/en
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC6474417/